Separation and loss are events of major importance to psychiatrists. Affective disorders are frequently preceded by important separations, and there is now data implicating separations and losses as etiologically significant antecedents of a variety of non-psychiatric medical disorders. Pilot data from our lab has demonstrated an impaired lymphocyte proliferative response to mitogen stimulation following peer and maternal separation in young monkeys; this data supports Bartrop et al.'s (1976) finding of decreased lymphocyte response to mitogen stimulation in bereaved human adults. We here propose a comprehensive series of prospective experiments designed to further study of the effects of separation and loss on the function of the immune system. Our working hypothesis is that separation or loss, i.e., the disruption of an attachment bond, may be accompanied by altered immune status resulting in organisms being at higher risk for the development of a variety of disorders. Using non-human primate mother-infant separation paradigms, we will evaluate the effects of loss and separation on several measures of cellular and humoral immune function, including the production of specific antibodies, lymphocyte proliferative responses to mitogens and antigens, B and T cell enumeration, and neutrophil function (chemotaxis and phagocytosis). Cortisol levels will also be determined. These studies should improve our understanding of the increase in morbidity and mortality that follows bereavement and other major losses in man, expand our knowledge of the complex organismic reaction to separation as an antecedent to affective disorders, and promote the development of a comprehensive theory of the pathophysiology of grief.